- General Drug Summary
- Description
- A metallic element of atomic number 30 and atomic weight 65.38. It is a necessary trace element in the diet, forming an essential part of many enzymes, and playing an important role in protein synthesis and in cell division. Zinc deficiency is associated with anemia, short stature, hypogonadism, impaired wound healing, and geophagia. It is known by the symbol Zn.
- Categories
- Trace Elements
- Structure
- Summary In Neonatal Jaundice
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2 record(s) for Zinc NA in Neonatal Jaundice.
- PMID
- Drug Name
- Efficacy
- Evidence
- Summary
- the tin and zinc porphyrin complexes have therapeutic potential for the treatment of Neonatal jaundice.
- Developmental biology of heme oxygenase. Clinics in perinatology, 1990 Jun [Go to PubMed]
- The regulation of heme oxygenase activity in the developing neonate is essential to the control of bilirubin production as well as intracellular heme and hemoprotein metabolism. The coordinated activity of the microsomal enzymes, heme oxygenase and NADPH-cytochrome c (P450) reductase, and the cytosolic enzyme biliverdin reductase is responsible for the degradation of heme. The complete reaction sequence requires oxygen and NADPH, and produces bilirubin and carbon monoxide in equimolar amounts. Although heme oxygenase expresses a rather broad range of substrate affinities, the oxidative degradation of heme is exclusively alpha-specific. Heme oxygenase is found in several tissues, with significant activity levels in the liver, spleen, and erythropoeitic tissue. Heme oxygenase activity is inducible by heme and other metalloporphyrins, hormones, starvation, stress, toxins, and xenobiotics. Heme oxygenase induction is generally considered to be the result of an increased protein synthesis and gene transcription. his hypothesis is supported by recent studies of the heme oxygenase gene that identified inducer element binding sites responsive to metal administration, heat shock, and nutrient availability. In the developing fetus and neonate, hepatic heme oxygenase activity and mRNA levels are elevated above that of the adult. This suggests that the elevated heme catabolism observed in neonates may be associated with an increased transcription of the heme oxygenase gene. The apparent induction of hepatic heme oxygenase during the neonatal period is probably the result of tissue-specific and time-dependent transcriptional regulating factors including potentially hormones and heme. Several metalloporphyrins, such as the tin and zinc porphyrin complexes, inhibit heme oxygenase activity and thus have therapeutic potential for the treatment of neonatal jaundice. Recent studies suggest that the meso- and bis-glycol derivatives of these metalloporphyrins may be more potent inhibitors of heme oxygenase activity in vitro and in ivo than the protoporphyrin structures. As structural analogues of heme, however, these compounds may also have other less desirable effects on the regulation of heme and hemoprotein metabolism, particularly in the developing neonate.
- Summary
- zinc bis glycol deuteroporphyrin (ZnBG), or zinc protoporphyrin (ZnPP),are potential compounds for the treatment of Neonatal jaundice.
- Systemic effects of orally-administered zinc and tin (IV) metalloporphyrins on heme oxygenase expression in mice. Pediatric research, 2006 May [Go to PubMed]
- Some metalloporphyrins (Mps) inhibit heme oxygenase (HO), the rate-limiting enzyme in the production of bilirubin, and are potential compounds for the treatment of neonatal jaundice. We studied the safety and efficacy of Mps following oral administration. Adult HO-1-luc reporter mice were administered 30 micromol/kg body weight of tin mesoporphyrin (SnMP), zinc bis glycol deuteroporphyrin (ZnBG), or zinc protoporphyrin (ZnPP), or vehicle by oral gavage. Bilirubin production was measured as total body carbon monoxide (CO) excretion (VeCO). HO activity was quantitated via CO measurements by gas chromatography. HO-1 protein was determined by Western blot. HO-1 transcription levels were assessed by in vivo bioluminescence imaging. A significant 28% decrease in bilirubin production occurred within 3 h of SnMP treatment and persisted beyond 48 h. Bilirubin production decreased 15% and 9% by 3 h after administration of ZnBG and ZnPP, respectively, but returned to baseline within 48 h. Maximal inhibition of liver, sleen, and intestine HO activity was seen at 3 h with inhibitory effects decreasing in the order: SnMP > or = ZnBG > or = ZnPP. After SnMP treatment, HO-1 transcription increased 5.7-fold after 24 h. Furthermore, liver and spleen HO-1 protein significantly increased 3.7- and 2.0-fold, respectively, after 24 h. HO-1 transcription and protein were not affected in ZnBG- or ZnPP-treated mice. We conclude that the three Mps are absorbed at different rates in the mouse and affect bilirubin production and HO-1 expression in a tissue- and time-dependent manner.
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5 record(s) for Zinc Effective in Inducing Remission in Neonatal Jaundice.
- PMID
- Drug Name
- Efficacy
- Evidence
- 8356009
- Zinc
- Effective in Inducing Remission
- Clinical Trial
- Summary
- May have a role in treating hyperbilirubinemia of the neonate.
- Targeting zinc protoporphyrin liposomes to the spleen using reticuloendothelial blockade with blank liposomes. Pediatric research, 1993 Jul [Go to PubMed]
- Metalloporphyrin inhibitors of heme oxygenase have been studied for use in the prevention of hyperbilirubinemia of the neonate. One report has suggested that incorporation of these drugs into liposomes can increase their localization to the spleen, dramatically reducing heme oxygenase activity in that important heme-degrading organ. We sought to further inrease porphyrin delivery to the spleen by using reticuloendothelial blockade with blank liposomes 2 h before injection of 0.3 microns extruded zinc protoporphyrin liposomes (L-ZnPP). Control adult rats without hemolysis had splenic heme oxygenase activity of 1.07 +/- 0.09 nmol carbon monoxide (CO)/h/mg protein. Rats treated with L-ZnPP alone had splenic heme oxygenase activity of 0.53 +/- 0.16 nmol CO/h/mg protein 6 h after L-ZnPP dosing. However, rats treated with 1000 mumol of blank liposomes per kg to saturate the reticuloendothelial system 2 h before L-ZnPP administration had splenic heme oxygenase activity of 0.25 +/- 0.16 nmol CO/h/mg protein at t = 6 h, which is significantly less than that of the L-ZnPP alone group (p < 0.05). In adult rats treated with heat-damaged red blood cells (RBC) to simulate hemolysis, treatment with 10 mumol of aqueous ZnPP per kg or 10 mumol of untargeted L-ZnPP per kg did not produce a difference from control in total body bilirubin production as estimated by CO excretion. However, RBC-treated rats given 1000 mumol of blank liposomes per kg 2 h before L-ZnPP administration produced significantly less CO than control, aqueous ZnPP-treated, and untargeted L-ZnPP-treated rats from 8 to 12 h after RBC treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
- 2380831
- Zinc
- Effective in Inducing Remission
- Clinical Trial
- Summary
- Effective, dose-dependent in vivo inhibitor of heme oxygenase in the newborn rhesus with latrogenic hemolysis and suppresses both bilirubin production and subsequent accumulation.
- Zinc protoporphyrin administration for suppression of increased bilirubin production by iatrogenic hemolysis in rhesus neonates. The Journal of pediatrics, 1990 Aug [Go to PubMed]
- We studied the effect of intravenous zinc protoporphyrin (ZnPP) administration on total body carbon monoxide excretion (VeCO), (an index of heme degradation), blood carboxyhemoglobin level, plasma bilirubin level, and tissue homogenate heme oxygenase activity 24 hours after delivery of rhesus neonates treated at 12 hours of age with heat-damaged erythrocytes (32 mumol heme/kg birth weight). All neonates were delivered by cesarean section and received ampicillin and gentamicin to suppress intestinal flora. The control group (n = 4) was treated with saline solution and ZnPP solvent; the erythrocyte-treated control group (n = 4) received erythrocytes and ZnPP solvent; and two experimental groups received erythrocytes and one dose of 10 (n = 3) or 40 (n = 4) mumol ZnPP/kg body weight, respectively. At 24 hours, administration of erythrocytes alone doubled the VeCO (p less than 0.05), carboxyhemoglobin level, (p less than 0.05), and plasma total bilirubin level (p less than 0.05). Treatment with ZnPP, 40 mumol/kgbody weight, caused a significant decrease in VeCO (p less than 0.05), carboxyhemoglobin (p less than 0.05), bilirubin (p less than 0.05), and spleen heme oxygenase (p less than 0.05). Treatment of the erythrocyte-loaded animals with ZnPP, 10 mumol/kg body weight, also significantly (p less than 0.05) lowered VeCO and spleen heme oxygenase activity but did not cause a significant lowering of blood carboxyhemoglobin or plasma bilirubin concentration. We conclude that ZnPP is an effective, dose-dependent in vivo inhibitor of heme oxygenase in the newborn rhesus with latrogenic hemolysis, and that it suppresses both bilirubin production and subsequent accumulation.
- 1772116
- Zinc
- Effective in Inducing Remission
- Clinical Trial
- Summary
- Zinc deuteroporphyrin 2,4-bis glycol acts as an inhibitor of adult Wistar rat tissue heme oxygenase (HO) activity and bilirubin production,also behaved as an in vitro photooxidizer by degrading and also enhanced the natural photodegradation of bilirubin.
- In vitro and in vivo characteristics of a heme oxygenase inhibitor: ZnBG. The American journal of the medical sciences, 1991 Dec [Go to PubMed]
- The authors evaluated the in vitro and in vivo efficacy and photosensitizing effects of zinc deuteroporphyrin 2,4-bis glycol (ZnBG) as an inhibitor of adult Wistar rat tissue heme oxygenase (HO) activity and bilirubin production. Concentrations of 0.02-0.05 microM ZnBG inhibited the HO activity in postmitochondrial supernatants of liver, spleen, brain, and kidney by at least 50%. Administration of 4 mumole ZnBG/kg body weight to adult rats significantly reduced the total body carbon monoxide (CO) excretion, an index of bilirubin formation, from 1 to 6 hours posttreatment. At 6 hours posttreatment, the HO activity in postmitochondrial supernatants of the liver and spleen, but not of the brain, was significantly lowered. ZnBG also behaved as an in vitro photooxidizer by degrading, in the presence of cool white light, the reduced form of nicotinamide adenine dinucleotide phosphate and histidine to CO and other nonidentified products. ZnBG also enhanced the natural photodegradation of bilirubin. Furthermore, admnistration of ZnBG to 1-day-old neonatal rats caused mortality within 12 hours in light-exposed animals, with a lethal dose 50 of 23 microM/kg body weight.
- 12395150
- Zinc
- Effective in Inducing Remission
- Review
- Summary
- Zinc bis-glycol porphyrin (ZnBG), a potent inhibitor of HO enzyme activity did not significantly affect HO-1 transcription and therefore may be well suited for the prevention of Neonatal jaundice.
- Selection of potential therapeutics based on in vivo spatiotemporal transcription patterns of heme oxygenase-1. Journal of molecular medicine (Berlin, Germany), 2002 Oct [Go to PubMed]
- Heme oxygenase (HO), a key catabolic enzyme in the conversion of heme to bilirubin, is an ideal target for reducing bilirubin production and preventing pathological jaundice in newborn infants. Metalloporphyrins (Mps) have been well characterized as competitive inhibitors of HO and have been evaluated as potential chemopreventive agents for neonatal jaundice. However, in addition to reducing HO activity, many Mps have been shown to increase HO-1 transcription, which would likely reduce their potential therapeutic utility. The differential effects of Mps on the transcription of HO-1 were therefore evaluated in living transgenic (Tg) reporter mice. Of the compounds evaluated, we observed that zinc bis-glycol porphyrin (ZnBG), a potent inhibitor of HO enzyme activity, did not alter HO-1 transcription patterns in Tg mice. Whole body images of HO-1 transcription patterns did, however; reveal increases in HO-1 transcription in Tg mice after treatment with other Mps, heme and cadmium chloride (CdCl(2)). Intravenousinjections of CdCl(2) resulted in expression patterns that differed in tempo and location from those observed in Tg mice treated with intraperitoneal injections. Spatiotemporal analyses of transcriptional regulation in living animals accelerated the assessment of an adverse effect of Mps by revealing different patterns of HO-1 transcription. Among the known inhibitors of HO enzyme activity that were evaluated in this study, ZnBG did not significantly affect HO-1 transcription and therefore may be well suited for the prevention of neonatal jaundice.
- 15699685
- Zinc
- Effective in Inducing Remission
- In Vitro Study
- Summary
- Oral administration of zinc salts efficiently decreased serum bilirubin levels in hyperbilirubinemic rats, presumably as a result of inhibition of enterohepatic circulation of bilirubin.
- The effect of zinc salts on serum bilirubin levels in hyperbilirubinemic rats. Journal of pediatric gastroenterology and nutritio, 2005 Feb [Go to PubMed]
- Intestinal metabolism of bilirubin is implicated in the pathogenesis of neonatal jaundice and Crigler-Najjar syndrome. In the present study the authors investigated the effect of oral administration of zinc salts on serum bilirubin levels in hyperbilirubinemic rats.
Bilirubin-binding activities of zinc sulfate and water-insoluble zinc methacrylate were determined in vitro. Congenitally hyperbilirubinemic Gunn rats and artificially hyperbilirubinemic Wistar rats were used in in vivo studies. Animals were fed a normal diet for 1 week and then a treatment diet of either zinc sulfate or zinc methacrylate for additional 2 weeks. Serum and fecal bile pigments were determined at the end of each phase. Biliary bilirubin secretion rates were determined in hyperbilirubinemic Wistar rats fed zinc methacrylate.
Substantial bilirubin-binding activities of zinc salts were demonstrated in in vitro experiments. Treatment with oral zinc salts significantly decreased serum bilirubin levels in Gunn rats (166 +/- 53 versus 123 +/- 38 and 206 +/- 34 versus 131 +/- 31 micromol/L, P < 0.05 for zinc methacrylate and zinc sulfate, respectively). A similar effect of zinc methacrylate was also observed in hyperbilirubinemic Wistar rats (102 +/- 10 versus 14 +/- 4 micromol/L, P < 0.0001). In accord, biliary bilirubin secretion decreased significantly in these animals (45 +/- 11 versus 28 +/- 4 nmol/h 100g body weight, P < 0.02). In contrast to zinc sulfate, treatment with zinc methacrylate did not lead to the elevation of serum zinc levels.
Oral administration of zinc salts efficiently decreased serum bilirubin levels in hyperbilirubinemic rats, presumably as a result of inhibition of enterohepatic circulation of bilirubin. This approach might be useful in the treatment of severe unconjugated hyperbilirubinemias.
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1 record(s) for Zinc Not Effective to Patients in Neonatal Jaundice.
- PMID
- Drug Name
- Efficacy
- Evidence
- 1467607
- Zinc
- Not Effective to Patients
- Clinical Trial
- Summary
- cord serum concentrations of zinc, magnesium or copper are not useful in predicting which neonates will develop hyperbilirubinemia.
- Predictive inability of cord zinc, magnesium and copper levels on the development of benign hyperbilirubinemia in the newborn. Acta paediatrica (Oslo, Norway : 1992), 1992 Nov [Go to PubMed]
- Cord serum concentrations of zinc, magnesium and copper were determined in 90 healthy term infants. The infants were divided by peak bilirubin values into an icteric group (peak bilirubin > 136 mumol/l) (n = 21) and a control group (peak bilirubin < or = 136 mumol/) (n = 69). Mean cord serum zinc, magnesium and copper concentrations in the icteric group did not differ from those of the control group. Furthermore, no significant correlation was found between peak serum bilirubin concentrations and cord serum concentrations of these three elements. We conclude that cord serum concentrations of zinc, magnesium or copper are not useful in predicting which neonates will develop hyperbilirubinemia.
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1 record(s) for Zinc Adverse Event in Neonatal Jaundice.
- PMID
- Drug Name
- Efficacy
- Evidence
- 6732121
- Zinc
- Adverse Event
- Clinical Trial
- Summary
- Zinc deficiency syndrome is related with neonatal jaundice.
- [Alagille's syndrome. Clinical and histo-pathologic study]. Annales de dermatologie et de vénéréologie, 1984 [Go to PubMed]
- Alagille 's syndrome, described in 1970, associates a chronic intrahepatic cholestasis (hypoplasia of the interlobulary biliary ducts), vertebral and visceral malformations, retarded physical, mental and sexual development and neonatal jaundice. A series of cutaneous manifestations are reviewed in their clinical, histological and ultrastructural aspects. Its relation with the zinc deficiency syndrome is discussed.